Anti-human TROP-2 antibody having anti-tumor activity in vivo

Abstract

The present invention provides: an antibody, which specifically reacts with hTROP-2 and has anti-tumor activity in vivo; a hybridoma, which produces the aforementioned antibody; a complex of the aforementioned antibody and a drug; a pharmaceutical composition for diagnosing or treating a tumor; a method for detecting a tumor; and a kit for detecting or diagnosing a tumor.

The invention claimed is: 
     
       1. An antibody against human TROP-2, which has anti-tumor activity in vivo, wherein the amino acid sequences of CDR 1 to 3 of the H chain V region of the antibody are shown in SEQ ID NOS: 36 to 38, respectively, and the amino acid sequences of CDR 1 to 3 of the L chain V region of the antibody are shown in SEQ ID NOS: 41 to 43, respectively. 
     
     
       2. The antibody according to  claim 1 , which exhibits 50% or more of tumor growth inhibitory activity at a dosage of 5 to 20 mg/kg body weight. 
     
     
       3. The antibody according to  claim 2 , wherein the frequency of administration for exhibiting the tumor growth inhibitory activity is at most once a week. 
     
     
       4. The antibody according to  claim 1 , which exhibits 50% or more of the tumor growth inhibitory activity by a single administration of the antibody at a dosage of 10 mg/kg body weight. 
     
     
       5. The antibody according to  claim 1 , which has anti-tumor activity on two or more types of human tumor cell lines. 
     
     
       6. The antibody according to  claim 5 , wherein the tumor cell lines are at least two types selected from the group consisting of a human pancreatic cancer cell line PK-59, a human pancreatic cancer cell line BxPC-3, a human pancreatic cancer cell line KP-3L, a human pancreatic cancer cell line KP-2, a human pancreatic cancer cell line PK-1, a human pancreatic cancer cell line PK-45H, a human pancreatic cancer cell line PK-45P, a human pancreatic cancer cell line TCC-PAN2, a human pancreatic cancer cell line SUIT-2, a human colon cancer cell line CACO-2, a human colon cancer cell line SW480, a human colon cancer cell line DLD-1, a human colon cancer cell line HCT 116, a human breast cancer cell line JIMT-1, a human breast cancer cell line HCC1143, a human breast cancer cell line MCF-7, a human prostate cancer cell line DU145 and a human prostate cancer cell line PC-3. 
     
     
       7. The antibody according to  claim 5 , wherein the tumor cell lines are the human pancreatic cancer cell line PK-59 and the human pancreatic cancer cell line BxPC-3. 
     
     
       8. The antibody according to  claim 1 , wherein the dissociation constant (Kd value) is 1.0×10 −10  M or less. 
     
     
       9. The antibody according to  claim 1 , which is a monoclonal antibody. 
     
     
       10. The antibody according to  claim 1 , wherein the tumor is at least one type selected from the group consisting of human pancreatic cancer, human prostate cancer, human colon cancer and human breast cancer. 
     
     
       11. The antibody according to  claim 1 , wherein the tumor is human pancreatic cancer. 
     
     
       12. The antibody according to  claim 1 , wherein the tumor is a recurrent cancer or a metastatic cancer. 
     
     
       13. The antibody according to  claim 1 , wherein the antibody is a genetically recombinant antibody. 
     
     
       14. The antibody according to  claim 13 , wherein the genetically recombinant antibody is a chimeric antibody, or a humanized antibody. 
     
     
       15. An antigen binding fragment derived from the antibody according to  claim 1 . 
     
     
       16. An antibody fragment-drug conjugate, which comprises the antibody fragment according to  claim 15  and a substance having anti-tumor activity and/or cell-killing activity. 
     
     
       17. The conjugate according to  claim 16 , wherein the tumor is at least one type selected from the group consisting of human pancreatic cancer, human prostate cancer, human colon cancer and human breast cancer. 
     
     
       18. The conjugate according to  claim 16 , wherein the tumor is a recurrent cancer of a metastatic cancer. 
     
     
       19. An antigen binding fragment derived from an antibody against human TROP-2, which has anti-tumor activity in vivo, wherein the fragment comprises the amino acid sequences shown in SEQ ID NOS: 36 to 38 and the amino acid sequences shown in SEQ ID NOS: 41 to 43. 
     
     
       20. The antigen binding fragment according to  claim 19 , which comprises the amino acid sequence shown in SEQ ID NO: 35 or the amino acid sequence consisting of amino acids at positions 20 to 134 in the amino acid sequence as shown in SEQ ID NO: 35 and the amino acid sequence shown in SEQ ID NO: 40 or the amino acid sequence consisting of amino acids at positions 21 to 127 in the amino acid sequence as shown in SEQ ID NO: 40. 
     
     
       21. An antibody-drug conjugate, which comprises the antibody according to  claim 1  and a substance having anti-tumor activity and/or cell-killing activity. 
     
     
       22. The conjugate according to  claim 21 , wherein the tumor is at least one type selected from the group consisting of human pancreatic cancer, human prostate cancer, human colon cancer and human breast cancer. 
     
     
       23. The conjugate according to  claim 21 , wherein the tumor is a recurrent cancer of a metastatic cancer. 
     
     
       24. A genetically recombinant antibody against human TROP-2, which is a chimeric antibody, or a humanized antibody, and has anti-tumor activity in vivo, wherein the H chain V region of the chimeric antibody consists of the amino acid sequence shown in SEQ ID NO: 35 or the amino acid sequence consisting of amino acids at positions 20 to 134 in the amino acid sequence as shown in SEQ ID NO: 35, and the L chain V region thereof consists of the amino acid sequence shown in SEQ ID NO: 40 or the amino acid sequence consisting of amino acids at positions 21 to 127 in the amino acid sequence as shown in SEQ ID NO: 40. 
     
     
       25. A monoclonal antibody against human TROP-2, which is produced by a hybridoma having accession No. FERM BP-11251. 
     
     
       26. A hybridoma producing a monoclonal antibody against human TROP-2, which has accession No. FERM BP-11251.